The principal objective of Project 1 is to establish whether psychosocial and lifestyle-related risk factors for cardiovascular disease are associated with individual differences in the reactivity of key neural structures underlying emotional processing and appetitive motivation. It is hypothesized that heightened reactivity of the amygdala to emotionally-relevant stimuli will covary with traits of neuroticism (or negative affectivity and affect- specific indicators of depression symptomatology, anxiety, and antagonistic disposition; autonomic, neuroendocrine and hemodynamic indices of potential relevance to cardiovascular risk; and to biomarkers of preclinical vascular disease and cumulative risk factor exposure. It is also hypothesized that heightened reactivity of the ventral striatum to reward-related stimuli will covary with psychometric indices of low conscientiousness, impulsivity, and intertemporal choice; with health risk behaviors (e.g., cigarette smoking, physical inactivity); metabolic syndrome and component risk factors, and carotid artery atherosclerosis. An additional aim is to identify genetic and environmental correlates of these two neural dimensions of individual differences. We propose to recruit a community sample of 530 men and women, 30-55 years of age and without clinical history of atherosclerotic cardiovascular disease. Subjects will participate in an fMRI neuroimaging protocol to assess amygdala and ventral striatal reactivities to behavioral stimuli, and data will be collected in each of the foregoing domains of behavioral and biological risk for cardiovascular disease. The latter will include a battery of diagnostic and assessment interviews and questionnaires, ambulatory physiological and behavioral monitoring, biological risk assessments, and ultrasound evaluations of carotid artery disease. In addition, blood for DNA analysis will be obtained from all study participants. Project 1 will provide the first systematic test of the hypothesis that individual differences in behavioral risk for cardiovascular disease may stem from functional variation in the reactivity of neural structures contributing to negative affect (threat sensitivity) and impulsive decision-making reward sensitivity). Support for this hypothesis will further our understanding of the origins of behavioral influences on heart disease and provide clues to possible commonalities of etiology and pathogenicity.